THIS COMPONENT IS ENTITLED THE GENOME ENGINEERING AND iPSC CENTER ABSTRACT GEiC Summary Statement/Abstract Genome engineering is a rapidly evolving field that enables the manipulation of complex genomes. Genome engineering uses custom endonucleases to create targeted double-strand breaks in genomic DNA. The repair of these DNA breaks by the natural cellular repair machinery can lead to targeted, user-defined genomic modifications enabling unprecedented abilities to study genetic variation and to manipulate cells for research and therapeutic purposes. These modifications can be anything from a targeted gene knockout to the precise change of a single nucleotide. For example, isogenic cell lines differing only by a single disease-associated variant (single nucleotide mutation, insertion or deletion) can be produced. Additionally, by injecting RNA encoding these custom endonucleases into a single-cell mouse embryo, investigators can rapidly produce genetically modified mice with the aforementioned genome manipulations. The system can also be used to produce other modified organisms (e.g. zebrafish, Drosophila, rats). Induced pluripotent stem cells (iPSCs) have the potential to develop into all tissues and organs of the human body, and therefore open new research avenues for disease modeling. Here, skin fibroblasts or renal epithelial cells from urine can be obtained from patients and reprogrammed into iPSCs, which in turn can be differentiated into a specific cell type to study pathogenesis associated with genetic mutations. Recent advances in genome editing using TALEN and CRISPR-based nucleases can be employed to ?repair? the disease mutation in the iPSC line generated for a specific patient. Alternatively these techniques allow rapid and facile introduction of disease-associated mutations into `normal' iPSCs so that a variety of disorders can be modeled without direct access to the patient's cells that harbor the specific mutation. This technology thus provides the ability to generate cells harboring a number of disease-causing mutations for screening purposes as well as cells that differ only at a single nucleotide for control purposes. To implement both the genome editing and iPSC technologies for use by biological and clinical scientists, we established the Genome Engineering and iPSC Center (GEiC) at Washington University with the goal of speeding scientific discovery through the rapid and precise modification of genomes. The GEiC is directed and staffed with scientists that together have over 25 years of genome engineering experience and 20 years of stem cell experience.